PHARMACOKINETIC-PHARMACODYNAMIC MODEL FOR SPIRAMYCIN IN STAPHYLOCOCCAL MASTITIS

Simultaneous pharmacokinetic-pharmacodynamic (PK/PD) modelling for spi ramycin in staphylococcal infections of the mammary gland of cows was used to predict the efficacy of spiramycin. A differential equation de rived from the Zhi model was fitted to an in vitro killing curve and p ost-antibiotic effect determination, A seven-compartment PK model, in which 4 compartments representing each quarter of the mammary gland wh ich was considered to be the effect compartment, was included, The PD model linked to the PK model was able to describe the in vivo spiramyc in effect against Staphylococcus aureus. The parameters calculated fro m in vitro data predicted a rapid decrease for the first 12-24 h, and regrowth within 72 h following the treatment, whereas in vivo the bact erial effect was much less after 24 h than that predicted by the in vi tro data, PK/PD modelling permitted the simulation of various doses to optimize the efficacy of the antibiotic, taking into account such dyn amic parameters as bacterial growth rate constant, bacterial killing r ate constant and the Michaelis-Menten type saturation constant. An opt imal dosage regimen of 20 000 IU/kg per day for 3 days was predicted f or the treatment of Staphylococcus aureus mastitis.